NON-MENDELIAN GENETICS

(1)

NON-MENDELIAN

GENETICS

(2)

Inheritance patterns are often more complex than predicted by simple Mendelian genetics

■ The relationship between genotype and phenotype is rarely as simple as in the pea plant characters Mendel studied

■ Many heritable characters are not determined by only one gene with two alleles

■ However, the basic principles of segregation and

independent assortment apply even to more complex

patterns of inheritance

(3)

Extending Mendelian Genetics for a Single Gene

■ Inheritance of characters by a single gene may deviate from simple Mendelian patterns in the following situations:

– When alleles are not completely dominant or recessive – When a gene has more than two alleles

– When a gene produces multiple phenotypes

(4)

Degrees of Dominance

■ Complete dominance occurs when phenotypes of the heterozygote and dominant homozygote are identical

■ In incomplete dominance, the phenotype of F

₁

hybrids is somewhere between the phenotypes of the two parental varieties

■ In codominance, two dominant alleles affect the phenotype

in separate, distinguishable ways

(5)

Figure 14.10-1

P Generation

Red White

Gametes

C

^W

C

^W

C

^R

C

^R

C

^R

C

^W

(6)

Figure 14.10-2

P Generation

F

₁

Generation

1

/

₂ ¹

/

₂

Red White

Gametes

Pink

Gametes

C

^W

C

^W

C

^R

C

^R

C

^R

C

^W

C

^R

C

^W

C

^R

C

^W

(7)

Figure 14.10-3

P Generation

F

₁

Generation

F

₂

Generation

1

/

₂ ¹

/

₂

1

/

₂ ¹

/

₂

1

/

₂

1

/

₂

Red White

Gametes

Pink

Gametes

Sperm

Eggs

C

^W

C

^W

C

^R

C

^R

C

^R

C

^W

C

^R

C

^W

C

^R

C

^W

C

^W

C

^R

C

^R

C

^W

C

^R

C

^R

C

^R

C

^W

C

^R

C

^W

C

^W

C

^W

(8)

■ A dominant allele does not subdue a recessive allele; alleles don’t interact that way

■ Alleles are simply variations in a gene’s nucleotide sequence

■ For any character, dominance/recessiveness relationships of alleles depend on the level at which we examine the

phenotype

The Relation Between Dominance and

Phenotype

(9)

■ Tay-Sachs disease is fatal; a dysfunctional enzyme causes an accumulation of lipids in the brain

– At the organismal level, the allele is recessive

– At the biochemical level, the phenotype (i.e., the

enzyme activity level) is incompletely dominant

– At the molecular level, the alleles are codominant

(10)

Frequency of Dominant Alleles

■ Dominant alleles are not necessarily more common in populations than recessive alleles

■ For example, one baby out of 400 in the United States is born

with extra fingers or toes

(11)

■ The allele for this unusual trait is dominant to the allele for the more common trait of five digits per appendage

■ In this example, the recessive allele is far more prevalent

than the population’s dominant allele

(12)

Multiple Alleles

■ Most genes exist in populations in more than two allelic forms

■ For example, the four phenotypes of the ABO blood group in humans are determined by three alleles for the enzyme (I) that attaches A or B carbohydrates to red blood cells: I

^A

, I

^B

, and i.

■ The enzyme encoded by the I

^A

allele adds the A carbohydrate, whereas the enzyme encoded by the I

^B

allele adds the B

carbohydrate; the enzyme encoded by the i allele adds

neither

(13)

Figure 14.11

Carbohydrate Allele

(a) The three alleles for the ABO blood groups and their carbohydrates

(b) Blood group genotypes and phenotypes Genotype

Red blood cell appearance

Phenotype (blood group)

A

B

B AB

none

O

I

^A

I

^B

i

I

^A

I

^B

ii

I

^A

I

^A

or I

^A

i I

^B

I

^B

or I

^B

i

(14)

Pleiotropy

■ Most genes have multiple phenotypic effects, a property called pleiotropy

■ For example, pleiotropic alleles are responsible for the

multiple symptoms of certain hereditary diseases, such as

cystic fibrosis and sickle-cell disease

(15)

Extending Mendelian Genetics for Two or More Genes

■ Some traits may be determined by two or more genes

(16)

Epistasis

■ In epistasis, a gene at one locus alters the phenotypic expression of a gene at a second locus

■ For example, in Labrador retrievers and many other mammals, coat color depends on two genes

■ One gene determines the pigment color (with alleles B for black and b for brown)

■ The other gene (with alleles C for color and c for no color)

determines whether the pigment will be deposited in the

hair

(17)

Figure 14.12

Sperm Eggs

9 : 3 : 4

1

/

₄ ¹

/

₄ ¹

/

₄ ¹

/

₄

1

/

₄

1

/

₄

1

/

₄

1

/

₄

BbEe BbEe

BE

bE

Be

be

BBEE BbEE BBEe BbEe

BbEE bbEE BbEe bbEe

BBEe BbEe BBee Bbee

BbEe bbEe Bbee bbee

(18)

Polygenic Inheritance

■ Quantitative characters are those that vary in the population along a continuum

■ Quantitative variation usually indicates polygenic

inheritance, an additive effect of two or more genes on a single phenotype

■ Skin color in humans is an example of polygenic inheritance

(19)

Integrating a Mendelian View of Heredity and Variation

■ An organism’s phenotype includes its physical appearance, internal anatomy, physiology, and behavior

■ An organism’s phenotype reflects its overall genotype and

unique environmental history

(20)

Many human traits follow Mendelian patterns of inheritance

■ Humans are not good subjects for genetic research – Generation time is too long

– Parents produce relatively few offspring – Breeding experiments are unacceptable

■ However, basic Mendelian genetics endures as the

foundation of human genetics

(21)

Pedigree Analysis

■ A pedigree is a family tree that describes the interrelationships of parents and children across generations

■ Inheritance patterns of particular traits can be traced

and described using pedigrees

(22)

Figure 14.15

Key

Male Female Affected

male Affected

female Mating Offspring

1st generation

2nd generation

3rd generation

1st generation

2nd generation

3rd generation

Is a widow’s peak a dominant or recessive trait?

(a) Is an attached earlobe a dominant

or recessive trait?

b) Widow’s

peak No widow’s

peak Attached

earlobe Free

earlobe FF or

WW Ff Ww or

Ww ww ww Ww

Ww ww ww Ww Ww ww

ww

Ff Ff Ff

Ff Ff ff

ff ff

FF or Ff ff

ff

(23)

Figure 14.15a

Widow’s

peak

(24)

Figure 14.15b

No widow’s

peak

(25)

Figure 14.15c

Attached

earlobe

(26)

Figure 14.15d

earlobe Free

(27)

■ Pedigrees can also be used to make predictions about future offspring

■ We can use the multiplication and addition rules to

predict the probability of specific phenotypes

(28)

Recessively Inherited Disorders

■ Many genetic disorders are inherited in a recessive manner

■ These range from relatively mild to life-threatening

(29)

The Behavior of Recessive Alleles

■ Recessively inherited disorders show up only in individuals homozygous for the allele

■ Carriers are heterozygous individuals who carry the recessive allele but are phenotypically normal; most individuals with recessive disorders are born to carrier parents

■ Albinism is a recessive condition characterized by a lack

of pigmentation in skin and hair

(30)

Figure 14.16

Parents Normal

Aa Sperm

Eggs

Normal Aa

Normal AA

Normal Aa (carrier) Normal Aa

(carrier)

Albino aa A

A

a

(31)

Figure 14.16a

(32)

■ If a recessive allele that causes a disease is rare, then the chance of two carriers meeting and mating is low

■ Consanguineous matings (i.e., matings between close relatives) increase the chance of mating between two carriers of the same rare allele

■ Most societies and cultures have laws or taboos against

marriages between close relatives

(33)

Cystic Fibrosis

■ Cystic fibrosis is the most common lethal genetic disease in the United States,striking one out of every 2,500 people of European descent

■ The cystic fibrosis allele results in defective or absent chloride transport channels in plasma membranes leading to a buildup of chloride ions outside the cell

■ Symptoms include mucus buildup in some internal organs and abnormal absorption of nutrients in the small

intestine

(34)

Sickle-Cell Disease: A Genetic Disorder with Evolutionary Implications

■ Sickle-cell disease affects one out of 400 African- Americans

■ The disease is caused by the substitution of a single amino acid in the hemoglobin protein in red blood cells

■ In homozygous individuals, all hemoglobin is abnormal (sickle-cell)

■ Symptoms include physical weakness, pain, organ

damage, and even paralysis

(35)

Fig. 14-UN1

■ Heterozygotes (said to have sickle-cell trait) are usually healthy but may suffer some symptoms

■ About one out of ten African Americans has sickle cell trait, an unusually high frequency of an allele with detrimental effects in homozygotes

■ Heterozygotes are less susceptible to the malaria parasite,

so there is an advantage to being heterozygous

(36)

Dominantly Inherited Disorders

■ Some human disorders are caused by dominant alleles

■ Dominant alleles that cause a lethal disease are rare and arise by mutation

■ Achondroplasia is a form of dwarfism caused by a rare

dominant allele

(37)

Figure 14.17

Parents Dwarf

Dd Sperm

Eggs

Dwarf Dd dd Normal

Dwarf Dd dd Normal D

d

Normal

dd

(38)

■ The timing of onset of a disease significantly affects its inheritance

■ Huntington’s disease is a degenerative disease of the nervous system

■ The disease has no obvious phenotypic effects until the individual is about 35 to 40 years of age

■ Once the deterioration of the nervous system begins the condition is irreversible and fatal

Huntington’s Disease: A Late-

Onset Lethal Disease

(39)

Genetic Testing and Counseling

■ Genetic counselors can provide information to prospective parents concerned about a family history for a specific

disease

(40)